Weight Changes From Glucagon‐Like Peptide‐1 Receptor Agonist Use and Discontinuation: A Retrospective Cohort Study

ABSTRACT Objective This study aimed to quantify the effect of glucagon‐like peptide‐1 receptor agonists (GLP‐1s) on weight loss and weight gain following GLP‐1 discontinuation. Methods This retrospective cohort study using electronic health records from TriNetX included individuals age 18 years or older with various lengths of continuous GLP‐1 use between September 2014 and November 2023. Applying an intention‐to‐treat framework, we used linear mixed effects models and propensity score adjustment to model changes in BMI after GLP‐1 discontinuation while accounting for correlated within‐person observations and potential confounders. Results A total of 78,076 (19.7%) individuals used GLP‐1s continuously for 3 months, 23,861 (6.0%) for 6 months, and 12,642 (3.2%) for 9 months. The median BMI prior to initiation was 36.38 (IQR 36.30–36.46), which declined by 2.15% (IQR 2.10%–2.21%) to 35.81 (IQR 35.7–35.92) among individuals with 3 months of continuous GLP‐1 use. Median BMI declines were greater among individuals with 6 months (4.38%, IQR 4.27%–4.48%) and 9 months (5.56%, IQR 5.34%–5.78%) of continuous use. On average, weight loss among discontinuers at months 3, 6, and 9 slowed in comparison to their counterparts. Conclusions Among this real‐world sample, GLP‐1 use was associated with more modest weight loss than has been demonstrated in randomized controlled trials.